Neoplasia

Cause of Neoplasia

In dogs, tumors of the large intestine are more common than tumors of the stomach and small intestine. The mean age of dogs affected with colonic neoplasia is variably reported between 7 and 11 years of age. Most colonic tumors of dogs are malignant and include the adenocarcinomas, lymphosarcomas, and gastrointestinal stromal tumors (leiomyosarcoma, neurofibrosarcoma, fibrosarcoma, and ganglioneuroma). Leiomyosarcomas are the most common (91 %) of the gastrointestinal stromal tumors. Most colonic neoplasia develop in the descending colon and rectum, although leiomyosarcomas more frequently develop in the cecum. Local tumor invasion apparently occurs at a slower rate with canine colonic neoplasia, and metastasis to distant sites is relatively uncommon. Benign colonic neoplasia (e. g., adenomas, adenomatous polyps, leiomy-oma’s) also occur, although they are less common than malignant tumors. Malignant transformation of adenomatous polyps to carcinoma in situ and invasive adenocarcinoma has been demonstrated in the dog just as it has in humans. Mb Extramedullary plasmacytomas are an uncommon tumor of the gastrointestinal tract but occur in the large intestine and rectum. All of the aforementioned tumors are associated with signs of inflammation and obstruction (i. e., hematochezia, tenesmus, dyschezia). Carcinoids (rare 5-hydroxytryptamine (5-HT]-secreting tumors) are occasionally associated with diarrhea because of the effects of 5-HT on secretion and motility.

In cats, adenocarcinoma (46%) is the most common tumor of the large intestine, followed by lymphosarcoma (41%) and mast cell tumors (9%). The mean age of cats affected with colonic neoplasia is 12.5 years. The descending colon (39%) and the ileocolic sphincter (28%) are the most common sites of colonic neoplasia in the cat. Unlike colonic tumors in the dog, feline colonic tumors have a high rate (63%) of metastasis and, of course, metastasis is associated with decreased survival time. Metastatic sites include colonic lymph nodes, mesenteric lymph nodes, liver, spleen, bladder, urethra, omentum, meso-colon, lungs, duodenum, and peritoneum.

Neoplasia: Pathophysiology

Mechanical obstruction is the most common pathophysiologic consequence of locally invasive colonic tumors. Other non-neoplastic processes such as intussusception, FIP granuloma, fibrosing stricture, linear and nonlinear foreign bodies, hematoma, and phycomycosis lesions also cause intraluminal obstruction. Prolonged obstruction induces smooth muscle hypertrophy proximal to the site of the obstruction. Other pathophysiologic consequences of intestinal obstruction are pronounced fluid secretion and malabsorption of water and solutes; fluid, electrolyte, and acid-base disturbances; proliferation and translocation of luminal bacteria; and inflammation, devitalization, and perhaps even perforation of the colon. Secretory diarrheas have been reported with carcinoids of the rectum, colon, and intestine.

Clinical Examination

Most affected dogs have signs of hematochezia, mucoid feces, tenesmus, and dyschezia of varying severity. Importantly, the clinical signs observed with colorectal neoplasia are often indistinguishable from other causes of obstruction or chronic colitis. Hematochezia is infrequently reported with leiomyosarcomas or leiomyomas, presumably because these tumors do not typically involve the mucosa. Other clinical signs depend on the tumor type and location. Vomiting, malabsorption, and cachexia may be observed, for example, when multifocal or diffuse tumors (e. g., lymphosarcoma) involve the proximal portions of the gastrointestinal tract. Gastrointestinal stromal tumors, particularly the leiomyomas, have been associated with hypoglycemia and the resulting clinical signs of muscular weakness and seizure activity. Functional plasmacytomas secrete a single class of immunoglobulin and affected animals may go on to develop hyperviscosity syndrome (e. g., retinal bleeding, epistaxis). If colonic perforation has occurred, animals may be presented moribund with fever, lethargy, anorexia, vomiting, abdominal pain, and collapse.

Vomiting (65%), diarrhea (52%), and weight loss (46%) are common clinical signs in cats with colonic neoplasia. Most cats with colonic (and alimentary) lymphosarcoma are FeLV-negative. These lymphomas are thought to be caused by FeLV, with integrated virus causing neoplastic transformation in the absence of viral replication. Although most lymphomas in cats appear to be comprised of malignant T lymphocytes, most colonic (and alimentary) lymphomas are of B cell origin. Alimentary and colonic lymphomas originate primarily from submucosal lymphocytes, mucosal lymphoid follicles, or both, although one recent study reported an epitheliotropic form of T cell intestinal lymphomas. Epitheliotropic T cell lymphomas have not yet been reported in the feline colon.

Diagnosis of Neoplasia

Canine rectal adenocarcinomas are palpable in 60% to 80% of clinical cases, but colonic and cecal lesions are not as readily apparent on physical examination. More than 50% of cats with colonic masses have a palpable abdominal mass.

Survey and contrast radiographic and ultrasonographic studies have been used with varying levels of success in the diagnosis of canine and feline colonic neoplasia. Annular stenotic lesions associated with adenocarcinoma of the colon may manifest as proximal colonic dilation on survey radiographs.

Radiographic contrast material more precisely outlines the narrowing of the lumen at the site of the tumor. Although still of some clinical utility, contrast studies have been largely superceded by ultrasonography and other imaging modalities. Ultrasonography is presently considered to be the most effective means of diagnosing colonic tumors in dogs and cats and appears to be useful in evaluating mural lesions and associated abdominal changes such as lymphadenopathy. Ultrasonography was reported to be useful 84% of the time in localizing feline colonic neoplasia in one study. Ultrasonographic features of colonic tumors include transmural wall thickening with complete loss of the normal wall layering, fluid accumulation proximal to the lesion, and reduced regional motility. Transabdominal fine needle aspiration, peritoneal fluid cytology, and endoscopic exfoliative cytology may be useful in the diagnosis of lymphoma, but histopathology is generally required for a definitive diagnosis of other colonic neoplasia. CT and magnetic resonance imaging (MRI) scanning have not been sufficiently evaluated at this time for reasonable comparisons to be made with ultrasonography.

Flexible colonoscopy with mucosal biopsy is the preferred method of diagnosis for colonic neoplasia. Endoscopic abnormalities may include mass effect, mucosal bleeding, increased mucosal friability, erosions and ulcers, and circumferential luminal narrowing with submucosal infiltrative lesions. Multiple biopsy specimens should always be taken from diseased tissue, adjacent healthy tissue, and the transition zone between healthy and diseased tissue. With tumor necrosis, the pathologist will have a much better chance of diagnosing and staging the disease by evaluating non-necrotic tissue.

Treatment of Neoplasia

The treatment of colonic neoplasia will depend upon tumor type, anatomic location, and presence and extent of metastases. Complete surgical excision is the recommended therapy for focal adenocarcinomas, cecal leiomyosarcomas, and obstructive lymphomas. Multiagent chemotherapy (prednisone, vincristine, cyclophosphamide) has been used to treat colonic lymphoma, but it does not appear to alter survival time in affected cats. Cyclo-oxygenase II (COX II) up-regulation may contribute to the growth characteristics of some canine colonic neoplasia. Selective COX II inhibitors (e. g., piroxicam, meloxicam) may therefore be useful in the treatment of some canine colonic neoplasia. Plasmacytomas may be managed with adjuvant chemotherapy (e. g., prednisone, melphalan) after surgical excision. Radiation therapy has been used to palliate recurrent adenocarcinomas with varying results and complications; however, postradiation peritonitis and perforation have been reported in some cases.

Prognosis of Neoplasia

The prognosis for adenomatous polyps, leiomy-omas, and fibromas is generally favorable. Adenocarcinomas, lymphosarcomas, and plasmacytomas tend to recur, metasta-size, or both to distant sites. Dogs with annular colorectal adenocarcinomas have a particularly poor prognosis with a median survival time (MST) of only 1.6 months. The prognosis for most malignant tumors is generally guarded. Surgical resection alone results in 22 month (dogs) and 15 month (cats) average survival times in dogs and cats. It should be noted that cats undergoing subtotal colectomy for colonic adenocarcinoma had a longer survival time than those receiving mass resection only (MST of 138 days versus 68 days). Not surprisingly, cats with metastatic lesions had much shorter survival times, 49 days versus 259 days.